The use of model genetic systems had its beginnings in the earliest days of the science of genetics and, as a result of the tremendous value of such systems in understanding genetic phenomena, continues in the present. Researchers often use in their work organisms which have short life spans, limited space requirements, and relatively small genomes. Specifically, certain species of worms, fruit flies, and yeast cells are common subjects of research. Using such organisms, researchers may learn the function of the various genes found within the DNA of the organisms. One commonly used method is to generate mutations in the genome of an organism, followed by selection or screening for those mutations which confer a specific property or characteristic to the organism. These mutational studies suggest probable functions for the genes in which mutations occur. Mutations often occur when a gene is changed in such a way that the product of the gene is altered or nonfunctional.
A common method for generating mutations uses transposable elements. Transposable elements are segments of DNA which have the ability to “hop”—that is, to be excised from their initial position in the DNA and move to a new location. In doing this, a transposable element, also known as a transposon, may insert into some portion of a gene, thus disrupting or even changing the function of the gene. Further, additional mutations may be created by remobilizing the transposon. Since this remobilization often occurs imperfectly, changes are created in the DNA sequence, leaving the final sequence different from the original sequence. See J. D. Watson, J. Witkowski, M. Gilman, and M. Zoller, Recombinant DNA 175–190, 439–440 2d. ed. (1996).
The P element, a transposable element found in the genes of fruit flies, see, e.g., A. C. Spradling, G. M. Rubin, Science 218, 341 (1982); J. D. Watson, J. Witkowski, M. Gilman, and M. Zoller, Recombinant DNA 175, 177 2d. ed. (1996), has been an enormously useful tool in Drosophila genetic analysis for two reasons. First, these transposons have been used for insertional mutagenesis. Mutagenic insertions constitute molecular tags that are used to rapidly clone the mutated gene. L. Cooley, R. Kelley, A. Spradling, Science 239, 1121 (1988). Particularly helpful in such studies is the presence of strains that lack any copies of the transposon. Second, P elements are used to introduce single copies of foreign sequences into the host genome. This feature is particularly useful for the rapid identification of gene expression patterns by using enhancer traps. H. J. Bellen, et al., Genes Dev. 3, 1288 (1989). The availability of such techniques would be particularly advantageous in studies of the genome of the nematode C. elegans. 
C. elegans is a model system in which genetics can be used to identify genes and biological pathways which are conserved between nematodes and vertebrates, and which thus constitute potential targets for the treatment of various diseases. C. elegans is particularly advantageous for genetic studies because it is easily propagated and because the genetic and physical maps of its genome are well-characterized. W. B. Wood, Introduction to C. elegans Biology (1988). The characterization of gene structure in C. elegans has become routine, largely through the efforts of the C. elegans genome project. The workers involved in this effort have cloned the entire genome into cosmid or YAC vectors and have completed the genomic sequence. C. elegans Sequencing Consortium, Science 282:2012–2018 (1998); A. Coulson et al., Proc. Natl. Acad. Sci. USA 83:7821–7825 (1986); A. Coulson et al., Bioessays 13:413–417 (1991); R. Wilson et al., Nature 368:32–38 (1994).
Standard mutagenesis in C. elegans employs chemical mutagens. After generation of a mutant, identification of the gene requires time-consuming genetic mapping followed by single gene rescue. Alternatively, transposon-based mutagenesis has been attempted using mutant backgrounds like mut-2, but efficiency of transposition is low and not specific for a defined transposon class. Further, since the genomes of all C. elegans strains contain transposons, it is very difficult to identify relevant insertions. Thus, utility of native transposons for regulated transposition in C. elegans is limited. First, all strains contain multiple copies of these transposons and thus new insertions do not provide unique tags. Second, mutator strains tend to activate the transposition of several classes of transposons, so that the type of transposon associated with a particular mutation is not known. Third, transposition is not regulated and the transposon tag can be lost by excision in subsequent generations. Fourth, attempts to regulate transposase expression have failed because expression of transgenes in the germline of C. elegans is very difficult. Although one could theoretically regulate the transposition of a specific element by expressing the transposase under the control of a germline-specific promoter, transgenic arrays are typically silenced in the germline. W. G. Kelly, S. Xu, M. K. Montgomery, A. Fire, Genetics 146, 227 (1997).
Another problem in this field is the difficulty of expressing DNA in the C. elegans germline. Current methods, see, e.g., W. G. Kelly et al., Genetics 146:227–238 (1997), are not adequate. First, current methods for expressing foreign DNA in the C. elegans germline do not work for all genes. Second, expression of genes introduced using these methods declines over time.
Finally, introduction of single copy DNA is not possible using existing technology.
From the foregoing, it will be appreciated that it would be a significant advancement in the art to provide methods that allow regulated expression of foreign DNA in the C. elegans germline. It would be a further advancement to provide methods that allow germline expression of a transgene in C. elegans. It would be a further advancement in the art to provide regulated expression of such a transgene in the germline, as by regulation using a heat-shock promoter. It would be a further advancement to provide methods of regulating the transposition of either endogenous or heterologous transposons in C. elegans. Further, it would be an advancement to provide transgene constructs to facilitate germline expression of transgenes and regulated transposition of homologous and heterologous transposons. Such compositions of matter and methods are disclosed herein.